About
32
Publications
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266
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Introduction
Milorad Dragić is a young, enthusiastic researcher with interest in purinergic signalling in neurodegenerative disorders. His PhD research is focused on changes in both, activity and expression of hippocampal CD73, CD39, CD39L1 and A1, A2A and A3 receptors in trimethyltin-induced neurodegenration, an animal model of Alzheimer-like disease.
Current institution
Additional affiliations
May 2021 - present
Position
- Teaching Assistant
Description
- Our group aims to resolve how purinergic signaling contributes to the interaction between neurons, glial cells and peripheral immune cells in the onset and progression of acute and chronic neuroinflammation. In particular, we study the involvement of ectonucleotidases, E-NTPDases1-3 and ecto-5′-nucleotidase and their complex regulation at the neurovascular unit, leading to the resolution of an acute neuroinflammatory response or to the progression to the chronic neuroinflammation.
April 2018 - present
Faculty of Biology University of Belgrade
Position
- Research Assistant
Education
October 2017 - July 2020
Publications
Publications (32)
Intermittent theta burst stimulation (iTBS), a protocol of repetitive transcranial magnetic stimulation, has shown potential therapeutic benefits in various neurological and neuropsychiatric disorders. Given its potential anxiety-relieving and pro-cognitive effects, we aimed to investigate the effects of a 7-day stimulation protocol or sham treatme...
The present study shows that animals with experimental autoimmune encephalomyelitis (EAE) exhibit olfactory dysfunction and impaired general cognitive abilities, as well as anxiety-like behavior. Olfactory dysfunction occurs on average at 2 dpi, well before the onset of the first motor signs of EAE (8–10 dpi). After the initial olfactory dysfunctio...
Exposure to the neurotoxin trimethyltin (TMT) selectively induces hippocampal neuronal injury and astrocyte activation accompanied with resultant neuroinflammation, which causes severe behavioral, cognitive, and memory impairment. A large body of evidence suggests that flaxseed oil (FSO), as one of the richest sources of essential omega-3 fatty aci...
JOURNAL/nrgr/04.03/01300535-202507000-00027/figure1/v/2024-09-09T124005Z/r/image-tiff
An imbalance in adenosine-mediated signaling, particularly the increased A 2A R-mediated signaling, plays a role in the pathogenesis of Parkinson’s disease. Existing therapeutic approaches fail to alter disease progression, demonstrating the need for novel approac...
Parkinson's disease is characterized neuropathologically by the degeneration of dopaminergic neurons in the ventral midbrain, the accumulation of α-synuclein (α-syn) aggregates in neurons and chronic neuroinflammation. In the past two decades, in vitro, ex vivo and in vivo studies have consistently shown the involvement of inflammatory responses me...
Fear-related disorders, including post-traumatic stress disorder (PTSD), and anxiety disorders are pervasive psychiatric conditions marked by persistent fear, stemming from its dysregulated acquisition and extinction. The primary treatment for these disorders, exposure therapy (ET), relies heavily on fear extinction (FE) principles. Adolescence, a...
Experimental autoimmune encephalomyelitis (EAE) is widely used animal model of multiple sclerosis (MS). The disease is characterized by demyelination and neurodegeneration triggered by infiltrated autoimmune cells and their interaction with astrocytes and microglia. While neuroinflammation is most common in the spinal cord and brainstem, it is less...
Parkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their applicability to humans. Alt...
Parkinson’s disease (PD) is manifested by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and caudoputamen (Cp), leading to the development of motor and non-motor symptoms. The contribution of oxidative stress to the development and progression of PD is increasingly recognized. Experimental models show that...
Ecto‐5′‐nucleotidase/CD73 (eN/CD73) is a membrane‐bound enzyme involved in extracellular production of adenosine and a cell adhesion molecule involved in cell–cell interactions. In neuroinflammatory conditions such as experimental autoimmune encephalomyelitis (EAE), reactive astrocytes occupying active demyelination areas significantly upregulate e...
Three novel cytosine-derived α,β-methylene diphosphonates designated MRS4598, MRS4552, and MRS4602
were tested in the range of 1 × 10- 9 to 1 × 10- 3 M for their efficacy and potency in inhibiting membrane-bound
ecto-5′-nucleotidase/CD73 activity in primary astrocytes in vitro. The compounds were also tested for their ability
to attenuate the react...
Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the progressive degeneration of the dopaminergic system, leading to a variety of motor and nonmotor symptoms. The currently available symptomatic therapy loses efficacy over time, indicating the need for new therapeutic approaches. Repetitive transcranial...
Introduction
Intracerebroventricularly (icv) injected streptozotocin (STZ) is a widely used model for sporadic Alzheimer’s disease (sAD)-like pathology, marked by oxidative stress-mediated pathological progression. Intermittent theta burst stimulation (iTBS) is a noninvasive technique for brain activity stimulation with the ability to induce long-t...
Alprazolam (ALP), a benzodiazepine (BDZ) used to treat anxiety, panic, and sleep disorders, is one of the most prescribed psychotropic drugs worldwide. The side effects associated with long-term (mis)use of ALP have become a major challenge in pharmacotherapy, emphasizing the unmet need to further investigate their underlying molecular mechanisms....
D-galactose (d-gal) is broadly used in animal aging studies as its chronic administration mimics learning and memory impairments related to aging in humans. However, within the few studies that utilize chronic oral d-gal intake, none of them is focused on alteration in synaptic structure and function. We examined the effects of 6-weeks oral d-gal i...
The present study demonstrates altered topographic distribution and enhanced neuronal expression of major adenosine-metabolizing enzymes, i.e. ecto-5ʹ-nucleotidase (eN) and tissue non-specific alkaline phosphatase (TNAP), as well as adenosine receptor subtype A2A in the hippocampus and cortex of male rats from early to late adulthood (3, 6, 12 and...
Intracerebroventricularly (icv) injected streptozotocin (STZ) model of Alzheimer's disease (AD) is used to explore the effect of intermittent theta burst stimulation (iTBS) on astrocyte and microglia reactivity in selectively vulnerable brain regions and answer the question whether these changes are in the context of cognitive capacity. The iTBS is...
Ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2) hydrolyzes extracellular ATP to ADP, which is the ligand for P2Y1,12,13 receptors. The present study describes the distribution of NTPDase2 in adult rat brains in physiological conditions, and in hippocampal neurodegeneration induced by trimethyltin (TMT). The study also describes the regu...
Adenosine 5'-triphosphate (ATP) and other nucleotides and nucleosides, such as adenosine, are versatile signaling molecules involved in many physiological processes and pathological conditions in the nervous system, especially those with an inflammatory component. They can be released from nerve cells, glial cells, and vascular cells into the extra...
Neurodegeneration implies progressive neuronal loss and neuroinflammation further contributing to pathology progression. It is a feature of many neurological disorders, most common being Alzheimer’s disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation which modulates excitability of stimulated brain areas...
Extracellular purine nucleotides, such as adenosine 5'-triphosphate (ATP), are important modulators of hippocampal function and plasticity. In the extracellular space, ATP is inherently short-lived molecule, which undergoes rapid enzymatic degradation to adenosine by ectonucleotidases. Given that ectonucleotidases have distinct and overlapping dist...
The present study examined the involvement of purinergic signaling components in the rat model of hippocampal degeneration induced by trimethyltin (TMT) intoxication (8 mg/kg, single intraperitoneal injection), which results in behavioral and neurological dysfunction similar to neurodegenerative disorders. We investigated spatial and temporal patte...
Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach i...
Astrocytes are the first responders to noxious stimuli by undergoing cellular and functional transition referred as reactive gliosis. Every acute or chronic disorder is accompanied by reactive gliosis, which could be categorized as detrimental (A1) of beneficial (A2) for nervous tissue. Another signature of pathological astrocyte activation is dist...
Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by inflammatory processes in the central nervous system (CNS). Decades of research led to discovery of several disease-modifying therapeutics strategies with moderate success. Experimental autoimmune encephalomyelitis (EAE) is currently the most commonly used experimental model f...
Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in t...
Extracellular adenine nucleotides and nucleosides, such as adenosine-5'-triphosphate (ATP) and adenosine, are among least investigated signaling factors that participate in 17β-estradiol (E2)-mediated synaptic rearrangements in rodent hippocampus. Their levels in the extrasynaptic space are tightly controlled by ecto-nucleoside triphosphate diphosp...
Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) aros...
Purinergic signaling is the main synaptic and non-synaptic signaling system in brain. ATP acts as a fast excitatory transmitter, while adenosine sets a global inhibitory tone within hippocampal neuronal networks. ATP and adenosine are interconnected by ectonucleotidase enzymes, which convert ATP to adenosine. Existing data point to the converging r...
Enzyme histochemistry is a valuable histological method which provides a connection between morphology, activity, and spatial localization of investigated enzymes. Even though the method relies purely on arbitrary evaluations performed by the human eye, it is still wildly accepted and used in histo(patho)logy. Texture analysis emerged as an excelle...
Questions
Question (1)
Hello,
We have encountered a specific problem which we did not have up until now. There are two stain bands, which are on both sides of the PVDF membrane, almost equal in size. We did not change our protocol. We are casting hand-made gels 8% or 10%, using the same buffers, wet transfer 1h on +4 C, incubation with primary over night on +4 C and secondary 2h at room temperature. We have used different primary and secondary antibodies, we used blocking with Skim milk and with BSA, we changed all solutions, but we still have the same problem (picture in attch). Does anyone know what might be the problem or did anyone encountered similar situation?
Thank you for your help,
Best regards,
Milorad
